DFT and POM analyses of new synthesized armed pyrimidine-5-carboxylates as antitumor cytostatic agents

Abstract The research article reports a simple strategy through Vilsmeier Haack formylation for the synthesis of ethyl 1-formyl-1,2,3,6-tetrahydro-4-methyl-2-oxo/thioxo-6-phenylpyrimidine-5-carboxylates. The most facile position for the formylation in these dihydro pyrimidines (DHPMs) is 1-N position. Different spectral analysis was used to confirm the proposed structures of newly synthesized compounds. A broad range of human tumor cell lines; viz. Lung, Colon, Breast, Ovary, Prostate, Melanoma, CNS etc. were used to screen the synthesized compounds. POM computational studies were performed to discuss the atomic charges, molecular geometry, as well as the drug score analyses. It is found that the introduction of formyl group at N-1 position is not much beneficial for antitumor applications, in contrast to the introduction of –COOC2H5 residue at C-5 in pyrimidine, while cytostatic nature of the compounds is retained. The coexistence of two combined pharmacophore sites is indicated by the bioinformatic analyses. The cytostatic nature of all the substituted N-formyl derivatives is indicated by the values of IG50 > 100 µM. Based on the obtained cytostatic results; cytotoxicity of the pyrimidine core can be targeted in the future work, by hindering antiviral pharmacophore site with metal complexes formation.